Endogenous CSE/H2S system mediates TNF--induced insulin resistance in 3T3-L1 adipocytes

被引:27
作者
Huang, Ci-You [1 ]
Yao, Wei-Feng [1 ]
Wu, Wei-guo [1 ]
Lu, Yu-Lian [1 ]
Wan, Hui [1 ]
Wang, Wen [1 ]
机构
[1] Nanjing Med Univ, Dept Endocrinol, Affiliated Wuxi Hosp 2, Wuxi 214002, Jiangsu, Peoples R China
关键词
cystathionine gamma-lyase; hydrogen sulfide; TNF-alpha; insulin resistance; NECROSIS-FACTOR-ALPHA; HYDROGEN-SULFIDE; ADIPOSE-TISSUE; H2S; EXPRESSION; OBESITY; INFLAMMATION; MECHANISMS; MUSCLE; CELLS;
D O I
10.1002/cbf.2920
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Tumour necrosis factor- (TNF- )is a major contributor to the pathogenesis of insulin resistance associated with obesity and type 2 diabetes. It has been found that endogenous hydrogen sulfide (H2S) contributes to the pathogenesis of diabetes. We have hypothesized that TNF--induced insulin resistance is involved in endogenous H2S generation. The aim of the present study is to investigate the role of endogenous H2S in TNF--induced insulin resistance by studying 3T3-L1 adipocytes. We found that treatment of 3T3-L1 adipocytes with TNF- leads to deficiency in insulin-stimulated glucose consumption and uptake and increase in endogenous H2S generation. We show that cystathionine -lyase (CSE) is catalysed in 3T3-L1 adipocytes to generate H2S and that CSE expression and activity are upregulated by TNF- treatment. Inhibited CSE by its potent inhibitors significantly attenuates TNF--induced insulin resistance in 3T3-L1 adipocytes, whereas H2S treatment of 3T3-L1 adipocytes impairs insulin-stimulated glucose consumption and uptake. These data indicate that endogenous CSE/H2S system contributes to TNF--caused insulin resistance in 3T3-L1 adipocytes. Our findings suggest that modulation of CSE/H2S system is a potential therapeutic avenue for insulin resistance. Copyright (c) 2012 John Wiley & Sons, Ltd.
引用
收藏
页码:468 / 475
页数:8
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